Near-unity nuclear polarization with an open-source 129Xe hyperpolarizer for NMR and MRI.

The exquisite NMR spectral sensitivity and negligible reactivity of hyperpolarized xenon-129 (HP(129)Xe) make it attractive for a number of magnetic resonance applications; moreover, HP(129)Xe embodies an alternative to rare and nonrenewable (3)He. However, the ability to reliably and inexpensively produce large quantities of HP(129)Xe with sufficiently high (129)Xe nuclear spin polarization (P(Xe)) remains a significant challenge--particularly at high Xe densities. We present results from our "open-source" large-scale (∼1 L/h) (129)Xe polarizer for clinical, preclinical, and materials NMR and MRI research. Automated and composed mostly of off-the-shelf components, this "hyperpolarizer" is designed to be readily implementable in other laboratories. The device runs with high resonant photon flux (up to 200 W at the Rb D1 line) in the xenon-rich regime (up to 1,800 torr Xe in 500 cc) in either single-batch or stopped-flow mode, negating in part the usual requirement of Xe cryocollection. Excellent agreement is observed among four independent methods used to measure spin polarization. In-cell P(Xe) values of ∼90%, ∼57%, ∼50%, and ∼30% have been measured for Xe loadings of ∼300, ∼500, ∼760, and ∼1,570 torr, respectively. P(Xe) values of ∼41% and ∼28% (with ∼760 and ∼1,545 torr Xe loadings) have been measured after transfer to Tedlar bags and transport to a clinical 3 T scanner for MR imaging, including demonstration of lung MRI with a healthy human subject. Long "in-bag" (129)Xe polarization decay times have been measured (T1 ∼38 min and ∼5.9 h at ∼1.5 mT and 3 T, respectively)--more than sufficient for a variety of applications.

A portable single-sided magnet system for remote NMR measurements of pulmonary function.

In this work, we report initial results from a light-weight, low field magnetic resonance device designed to make relative pulmonary density measurements at the bedside. The development of this device necessarily involves special considerations for the magnet, RF and data acquisition schemes as well as a careful analysis of what is needed to provide useful information in the ICU. A homogeneous field region is created remotely from the surface of the magnet such that when the magnet is placed against the chest, an NMR signal is measured from a small volume in the lung. In order to achieve portability, one must trade off field strength and therefore spatial resolution. We report initial measurements from a ping-pong ball size region in the lung as a function of lung volume. As expected, we measured decreased signal at larger lung volumes since lung density decreases with increasing lung volume. Using a CPMG sequence with ΔTE=3.5 ms and a 20 echo train, a signal to noise ratio ~1100 was obtained from an 8.8mT planar magnet after signal averaging for 43 s. This is the first demonstration of NMR measurements made on a human lung with a light-weight planar NMR device. We argue that very low spatial resolution measurements of different lobar lung regions will provide useful diagnostic information for clinicians treating Acute Respiratory Distress Syndrome as clinicians want to avoid ventilator pressures that cause either lung over distension (too much pressure) or lung collapse (too little pressure).

Single-breath xenon polarization transfer contrast (SB-XTC): implementation and initial results in healthy humans.

PURPOSE: To implement and characterize a single-breath xenon transfer contrast (SB-XTC) method to assess the fractional diffusive gas transport F in the lung: to study the dependence of F and its uniformity as a function of lung volume; to estimate local alveolar surface area per unit gas volume S(A)/V(Gas) from multiple diffusion time measurements of F; to evaluate the reproducibility of the measurements and the necessity of B(1) correction in cases of centric and sequential encoding. MATERIALS AND METHODS: In SB-XTC three or four gradient echo images separated by inversion/saturation pulses were collected during a breath-hold in eight healthy volunteers, allowing the mapping of F (thus S(A)/V(Gas)) and correction for other contributions such as T(1) relaxation, RF depletion and B(1) inhomogeneity from inherently registered data. RESULTS: Regional values of F and its distribution were obtained; both the mean value and heterogeneity of F increased with the decrease of lung volume. Higher values of F in the bases of the lungs in supine position were observed at lower volumes in all volunteers. Local S(A)/V(Gas) (with a mean ± standard deviation of S(A)/V(Gas) = 89 ± 30 cm(-1)) was estimated in vivo near functional residual capacity. Calibration of SB-XTC on phantoms highlighted the necessity for B(1) corrections when k-space is traversed sequentially; with centric ordering B(1) distribution correction is dispensable. CONCLUSION: The SB-XTC technique is implemented and validated for in vivo measurements of local S(A)/V(Gas).

Novel MR Imaging Applications for Pleural evaluation.

Computed tomography is the first-line modality for evaluation of chest diseases primarily because of its spatial resolution. Magnetic resonance (MR) imaging is used as a problem-solving tool to answer key questions that are vital to optimal patient management. MR has the potential to provide qualitative, quantitative, anatomic, and functional information without the use of ionizing radiation or nephrotoxic contrast administration. With new advances in proton MR techniques, MR imaging can overcome some of the inherent problems associated with imaging the lung. This article describes novel MR applications for evaluation of the pleura and pleural diseases.

XeNA: an automated 'open-source' (129)Xe hyperpolarizer for clinical use.

Here we provide a full report on the construction, components, and capabilities of our consortium's "open-source" large-scale (~1L/h) (129)Xe hyperpolarizer for clinical, pre-clinical, and materials NMR/MRI (Nikolaou et al., Proc. Natl. Acad. Sci. USA, 110, 14150 (2013)). The 'hyperpolarizer' is automated and built mostly of off-the-shelf components; moreover, it is designed to be cost-effective and installed in both research laboratories and clinical settings with materials costing less than $125,000. The device runs in the xenon-rich regime (up to 1800Torr Xe in 0.5L) in either stopped-flow or single-batch mode-making cryo-collection of the hyperpolarized gas unnecessary for many applications. In-cell (129)Xe nuclear spin polarization values of ~30%-90% have been measured for Xe loadings of ~300-1600Torr. Typical (129)Xe polarization build-up and T1 relaxation time constants were ~8.5min and ~1.9h respectively under our spin-exchange optical pumping conditions; such ratios, combined with near-unity Rb electron spin polarizations enabled by the high resonant laser power (up to ~200W), permit such high PXe values to be achieved despite the high in-cell Xe densities. Importantly, most of the polarization is maintained during efficient HP gas transfer to other containers, and ultra-long (129)Xe relaxation times (up to nearly 6h) were observed in Tedlar bags following transport to a clinical 3T scanner for MR spectroscopy and imaging as a prelude to in vivo experiments. The device has received FDA IND approval for a clinical study of chronic obstructive pulmonary disease subjects. The primary focus of this paper is on the technical/engineering development of the polarizer, with the explicit goals of facilitating the adaptation of design features and operative modes into other laboratories, and of spurring the further advancement of HP-gas MR applications in biomedicine.

Inhalation heterogeneity from subresidual volumes in elite divers.

Punctate reopening of the lung from subresidual volumes (sub-RV) is commonly observed in excised lung preparations, either degassed or collapsed to zero transpulmonary pressure, and in the course of reinflation of human lungs when the chest is open, secondary to traumatic or surgical pneumothoraxes. In the course of physiological studies on two elite breath-hold divers, who are able to achieve lung volumes well below traditional RV with glossopharyngeal exsufflation, we used MRI lung imaging with inhaled hyperpolarized (129)Xe to visualize ventilatory patterns. We observed strikingly inhomogeneous inhalation patterns with small inhalation volumes from sub-RV, consistent with reopening of frankly closed airways. On the other hand, two age-matched and two older controls, inhaling from just above RV, showed a much more homogeneous pattern. Our results demonstrate the concept of frank airway closure below RV in young healthy adults with an intact chest wall.